Exercise is Good for the Brain

Judy L. Cameron, Ph.D.

University of PittsburghDept. of PsychiatryDept. of Obstetrics, Gynecology and Reproductive MedicineDirector, Outreach for the Clinical Translational Science InstituteandThe Oregon National Primate Research CenterSenior Scientist

Experimental Model:Rhesus monkeys and Cynomolgus monkeys

Bill GreenoughRunning wheelComplex environmentCage potato

Exercise Training Female Cynomolgus MonkeysThree experimental groupsRunners (run 5 months)Sedentary (sit 5 months)Run-Stops (run 5 mo, sit 3 mo)Running protocol80% max heart rate1 hr/day, 5 days/week20 weeks

Cognitive Testing: WGTA

Monkeys that exercise are more attentive, and learn to use the testing apparatus twice as fast.

What is the affect of being more alert and attentive while you are in school??

Running Increases Vascular Volume in the Motor Cortex of Older AnimalsSedentaryRunnerRun-StopBrdU-labeled endothelial cell

Running Increased Neurogenesis in the Hippocampus of Middle-aged MonkeysbIII tubulinBrdUMiddle age Older age*

Running Increased the Production of Astrocytes in the Motor CortexBrdUS100NeuNMiddle age Older age**

Exercise increases vascular volume in the cortex, neurogenesis in the hippocampus, and gliogenesis in many brain regions.Conclusions:Clinical Implications: Exercise may counteract changes in the brain with aging, and protect against neurodegenerative diseases (i.e., PD, AD, & stroke)

NeuroprotectiveEffects of ExerciseZhiming Zhang, Ph.D.Univ. KentuckyMichael Zigmond, Ph.D.Rehana Leak, Ph.D.Brian Lopresti, Ph.D.Chet Mathis, Ph.D.Univ. PittsburghKaroly Mirnics, Ph.D.Vanderbilt Univ.NINDS: R21 NS053471, P50 NS019608

Braak et al., 2004Lewy bodySubstantia nigraParkinsons Disease

Experimental DesignRunning (1 hr/day, 5 days/wk)[Sedentary, 60% max hr, 80% max hr]3 months MPTP(0.8 mg)Running/Sedentary1.5 monthsAdult, femaleRhesus monkeys(15-20 yrs. old)

Monkeys with Highest Levels of Physical Activity had the Least Damage to Nigrostriatal Dopamine Neurons

Monkeys with Highest Levels of Physical Activity had the Least Damage to Nigrostriatal Dopamine Neurons

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Being more active, regardless of the quantity of aerobic exercise undertaken, can protect DA neurons in the striatum from neurotoxic damageConclusions:Clinical Implications: Maintaining an active lifestyle may significantly protect the brain against neurodegenerative diseases (i.e., Parkinsons Disease), or be useful in decreasing the rate of progression of Parkinsons Disease. This is a health strategy that would be accessible to many people regardless of their baseline fitness.

Changes in the Brain with Normal ActivityElinor Sullivan, Ph.D.ONPRCKaroly Mirnics, Ph.D.Vanderbilt Univ.

Monkeys Have Been Fitted with Activity Monitors

There are LARGE individual differences in daily activity levels

Does General Activity Affect Health?

Monkeys put on a High Fat Diet Show Large Individual Differences in Weight Gain507090110130150170190Percent weight gainInitial WeightAfterOvx5 moHigh fat diet9 moHigh fat diet

Only Activity Predicts Body Weight Changein Adulthood024681012024681012p =0.03p =0.58p =0.14ActivityFood IntakeMetabolic RatePercent Change Body Weight024681012

Being more active is the best way to prevent adult weight gain.Conclusion:Clinical Implications: Maintaining an active lifestyle is very important for preventing adult weight gain and obesity. With 60% of the adult population in the United States overweight, increasing activity is critically important for prevention of obesity-related diseases including heart attacks, strokes, and diabetes.

Current and Future DirectionsWhat are the intracellular mechanisms by which exercise modulates neuronal function?

What are the differential effects of high activity vs. aerobic exercise?

Will exercise be useful as a therapy or adjunct therapy in treating:Substance abuse (smoking: Drs. Kupfer, Soreca and Monk)Depression and Bipolar Disorder (Drs. Kupfer, Frank)Neurodegenerative diseases (Drs. Zigmond, Zhang, Mirnics)Normal aging (Drs. Zigmond, Mirnics)

Physiological StudiesNathan RockcastleJoan Bytheway, Ph.D.Kris McCormickHenry LangeMatt JohnsonMaria Centeno, Ph.D.NeuroanatomySean KohlerJenny BoklewskiGeorgina AldridgeRobert Galvez

Biochemistry, Gene ExpressionAmanda Mitchell, Ph.D.Krassimira GarbettAmanda Smith, Ph.D.Sandra Castro

Questions?

*************causes of individual differences in weight gain and lossto investigate the individual differences in weight gain used 2 tools (ovx and HFD) to promote weight gain170 75%**